The goal of this research is to develop procedures and instrumentation for accurate bronchoscopic localization of carcinoma in situ, even when invisible on white-light inspection, and very small areas of bronchial mucosal carcinoma, not possible by routine fiberoptic bronchoscopy, in individuals with positive sputum cytology and negative chest X-ray. The imaging fluorescence bronchoscopy system employs violet light (410 nm) from a krypton ion laser and an image intensifier at the eyepiece through which, alternately and quickly, white-light and fluorescent light views of the bronchi can be seen. Clinical trials are being carried out at 4 hr and 72 hrs after a single intravenous injection of hematoporphyrin derivative (HpD) at 3.0 mg/kg dosage and other dosages (to 5.0 mg/kg). The potential of this method has been demonstrated in that in two patients, small (1-2 mm) areas of CIS were localized solely by their fluorescence, which areas visibly (white-light) showed normal appearing mucosa. Instrumentation is being developed to augment imaging fluorescence detection, consisting of a photometer probe to quantitatively measure fluorescence, a video analyzer system to measure the brightness of fluorescence of the images of lesions against background, by the real-time digital computer analysis to enhance contrast and sharpen edges of very small fluorescing areas, and by the real-time spectral analysis of HpD in suspected areas. (5)